Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)

Platts-Mills, James A; Babji, Sudhir; Bodhidatta, Ladaporn; Gratz, Jean; Haque, Rashidul; Havt, Alexandre; McCormick, Benjamin; McGrath, Monica; Olórtegui, Maribel Paredes; Samie, Amidou; Shakoor, Sadia; Mondal, Dinesh; Lima, Ila Fernanda Nunes; Hariraju, Dinesh; Rayamajhi, Bishnu Bahadur; Qureshi, Shahida; Kabir, Furqan; Yori, Pablo Peñataro; Mufamadi, Brenda; Amour, Caroline; Carreon, Joseph D.; Richard, Stephanie A; Lang, Dennis; Bessong, Pascal; Mduma, Esto; Ahmed, Tahmeed; Lima, Aldo A. M.; Mason, Carl J.; Zaidi, Anita K. M.; Bhutta, Zulfiqar A; Kosek, Margaret; Guerrant, Richard L.; Gottlieb, Michael; Miller, Mark A.; Kang, Gagandeep; Houpt, Eric R.

doi:10.1016/s2214-109x(15)00151-5

Cited by 768 publications

(862 citation statements)

References 37 publications

Supporting

Mentioning

754

Contrasting

Unclassified

Order By: Relevance

“…Enteric infections have long been recognized as a major cause of morbidity and mortality among young infants, and this burden is greatest in the developing countries where oral vaccines are least immunogenic [2,124]. Enteric infections present at the time of vaccination or in the period leading up to vaccination might impede oral vaccines in several ways.…”

Section: Enteric Infectionsmentioning

confidence: 99%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

View full text Add to dashboard Cite

Oral vaccines are less immunogenic when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Here, we review factors that might contribute to this phenomenon, including transplacental antibodies, breastfeeding, histo blood group antigens, enteric pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We highlight several clear risk factors for vaccine failure, such as the inhibitory effect of enteroviruses on oral poliovirus vaccine. We also highlight the ambiguous and at times contradictory nature of the available evidence, which undoubtedly reflects the complex and interconnected nature of the factors involved. Mechanisms responsible for diminished immunogenicity may be specific to each oral vaccine. Interventions aiming to improve vaccine performance may need to reflect the diversity of these mechanisms. Enteric pathogens are a substantial threat to public health. This threat takes many forms, from the toxin-producing bacteria (e.g., Vibrio cholerae) and flagellated protozoa (e.g., Giardia lamblia) that colonize the mucosal surface of the small intestine to the enteroviruses that are capable of spreading via the bloodstream to the CNS, causing acute flaccid paralysis (e.g., poliovirus). Each year, enteric pathogens cause hundreds of millions of cases of diarrhea and approximately 800,000 deaths, the vast majority of which occur among children in low-income countries [1]. The most common causes of childhood diarrheal morbidity include rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli and Shigella [2].Vaccines against enteric pathogens are important tools for mitigating this disease burden. Oral vaccines offer several distinct benefits compared with parenteral vaccines. They can be produced in large quantities at relatively low cost, are easy to administer and have the capacity to induce local immunity in the intestinal mucosa, thereby protecting vaccinated individuals against subsequent infection and -by blocking onward transmission -enhancing herd immunity [3,4]. Currently licensed oral vaccines include live-attenuated poliovirus vaccines containing one, two or three serotypes, live-attenuated rotavirus vaccines (Rotarix R , RotaTeq R , Lanzhou lamb rotavirus vaccine [China only] and Rotavac R [India only]), live-attenuated cholera vaccine (CVD 103-HgR or Vaxchora TM ), inactivated cholera vaccines (Dukoral R and Shanchol R ) and live-attenuated typhoid vaccine (Ty21a). Other oral vaccines are in development, including those against Shigella, enterotoxigenic E. coli, Campylobacter and Clostridium difficile, as well as several novel rotavirus vaccine candidates (including the human neonatal vaccine RV3-BB [5] and an oral bovine pentavalent vaccine [6]).Yet oral vaccines have an Achilles' heel -their immunogenicity and efficacy is impaired in low-income countries that experience the greatest burden of enteric disease (Box 1). For example, Rotarix has a 1-year protective efficacy against severe rotavirus-associated gas...

show abstract

Section: Enteric Infectionsmentioning

confidence: 99%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

View full text Add to dashboard Cite

show abstract

“…ryptosporidium exposure is a health hazard in almost all populations, particularly among children (1,2). While the infection is typically self-limited in immunocompetent adults, the very young and the immunocompromised often experience persistent and sometimes life-threatening infections.…”

mentioning

confidence: 99%

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

et al. 2016

View full text Add to dashboard Cite

e Cryptosporidium causes significant diarrhea worldwide, especially among children and immunocompromised individuals, and no effective drug treatment is currently available for those who need it most. In this report, previous volunteer infectivity studies have been extended to examine the association between fecal indole and indole-producing (IP) gut microbiota on the outcome of a Cryptosporidium infection. Fecal indole concentrations (FICs) of 50 subjects and 19 taxa of common gut microbiota, including six IP taxa (11 subjects) were determined in stool samples collected before and after a challenge with Cryptosporidium oocysts. At the baseline, the mean FIC (؎ the standard deviation) was 1.66 ؎ 0.80 mM in those who became infected after a challenge versus 3.20 ؎ 1.23 mM in those who remained uninfected (P ‫؍‬ 0.0001). Only 11.1% of the subjects with a FIC of >2.5 mM became infected after a challenge versus 65.2% of the subjects with a FIC of <2.5 mM. In contrast, the FICs of infected subjects at the baseline or during diarrhea were not correlated with infection intensity or disease severity. The relative abundances (percent) of Escherichia coli, Bacillus spp., and Clostridium spp. were greater >2.5-fold in volunteers with a baseline FIC of >2.5 mM, while those of Bacteroides pyogenes, B. fragilis, and Akkermansia muciniphila were greater in those with a baseline FIC of <2.5 mM. These data indicate that some IP bacteria, or perhaps indole alone, can influence the ability of Cryptosporidium to establish an infection. Thus, preexisting indole levels in the gut join the oocyst dose and immune status as important factors that determine the outcome of Cryptosporidium exposure.

show abstract

“…nterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of diarrheal illness in developing countries, where young children are most susceptible (1,2). In addition, these pathogens are also a common cause of diarrhea in immunologically naive travelers (3) who venture to areas of endemicity where sanitation and clean water remain limited.…”

mentioning

confidence: 99%

Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

Luo

Vickers

Fleckenstein

2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

c Enterotoxigenic Escherichia coli (ETEC) strains are a common cause of diarrhea. Extraordinary antigenic diversity has prompted a search for conserved antigens to complement canonical approaches to ETEC vaccine development. EtpA, an immunogenic extracellular ETEC adhesin relatively conserved in the ETEC pathovar, has previously been shown to be a protective antigen following intranasal immunization. These studies were undertaken to explore alternative routes of EtpA vaccination that would permit use of a double mutant (R192G L211A) heat-labile toxin (dmLT) adjuvant. Here, oral vaccination with EtpA adjuvanted with dmLT afforded significant protection against small intestinal colonization, and the degree of protection correlated with fecal IgG, IgA, or total fecal antibody responses to EtpA. Sublingual vaccination yielded compartmentalized mucosal immune responses with significant increases in anti-EtpA fecal IgG and IgA, and mice vaccinated via this route were also protected against colonization. In contrast, while intradermal (i.d.) vaccination achieved high levels of both serum and fecal antibodies against both EtpA and dmLT, mice vaccinated via the i.d. route were not protected against subsequent colonization and the avidity of serum IgG and IgA EtpA-specific antibodies was significantly lower after i.d. immunization compared to other routes. Finally, we demonstrate that antiserum from vaccinated mice significantly impairs binding of LT to cognate GM1 receptors and shows near complete neutralization of toxin delivery by ETEC in vitro. Collectively, these data provide further evidence that EtpA could complement future vaccine strategies but also suggest that additional effort will be required to optimize its use as a protective immunogen. Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of diarrheal illness in developing countries, where young children are most susceptible (1, 2). In addition, these pathogens are also a common cause of diarrhea in immunologically naive travelers (3) who venture to areas of endemicity where sanitation and clean water remain limited.Given the significant impact of ETEC on global health, a vaccine to prevent these infections is a significant priority (4). However, despite decades of investigative efforts following the discovery of toxin-producing E. coli in patients with clinical illnesses indistinguishable from cholera (5), a vaccine that affords broadbased protection has yet to be developed.All of the ETEC-specific virulence genes described to date are encoded on plasmids. These include the heat-labile and/or heatstable enterotoxins that define this pathovar and the colonization factors (CFs). Most vaccines to date have primarily targeted these colonization factors, which include a broad array of fimbrial as well as afimbrial surface antigens thought to be essential for intestinal colonization and/or heat-labile toxin.Unfortunately, the heterogeneity of CF antigenic structures presents a challenge to development of a broadly protective vaccine. ...

show abstract

Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)

Cited by 768 publications

References 37 publications

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

Contact Info

Product

Resources

About